Allogene Therapeutics Announces Positive Phase 1 Data Demonstrating the Potential of ALLO-316 in Heavily Pretreated Patients with Advanced Renal Cell Carcinoma at SITC and IKCS

• Phase 1 TRAVERSE Trial Demonstrated a Single Infusion of ALLO-316 Can Yield an Overall Response Rate of 50% and Confirmed Response Rate of 33% in Patients with CD70 Tumor Proportion Score (TPS) of Greater than 50%
• TRAVERSE Trial Highlights the Ability of CD70 Dagger^® Technology to Promote Robust Expansion and Persistence of ALLO-316 with Standard Lymphodepletion, Validating its Potential as the Next Generation Allogeneic Platform 
• ALLO-316 Demonstrated a Manageable Safety Profile; Newly Implemented Diagnostic and Management Algorithm Appears Highly Effective in Abating IEC-HS While Preserving CAR T Efficacy
• Data from the TRAVERSE Trial Supported the FDA’s Recent RMAT Designation for ALLO-316 as a Potential Treatment for Advanced or Metastatic RCC

SOUTH SAN FRANCISCO, Calif., Nov. 07, 2024 (GLOBE NEWSWIRE) — Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T^™) products for cancer and autoimmune disease, will concurrently present new data from the Phase 1 TRAVERSE trial in an oral presentation at the 2024 International Kidney Cancer Symposium (IKCS) and a poster session at The Society for Immunotherapy of Cancer’s (SITC) Annual Meeting. The trial evaluates ALLO-316, the Company’s first AlloCAR T product candidate for the potential treatment of solid tumors. The ongoing Phase 1 TRAVERSE trial is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy. These presentations highlight compelling evidence of CAR T activity and anti-tumor efficacy in 26 patients with RCC tumors known to be CD70 positive who were evaluable for efficacy outcomes.

“ALLO-316, the leading “off-the-shelf” CAR T product candidate currently in development for solid tumors, continues to show remarkable potency in the TRAVERSE trial. Data from the Phase 1 study demonstrating significant anti-tumor activity in patients with metastatic disease resistant to multiple therapeutic classes, even with standard lymphodepletion, potentially marks a major advancement in the field,” said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. “The unprecedented cell expansion and persistence driven by CD70 CAR-intrinsic Dagger^® technology, along with strong evidence of tumor infiltration by CAR T cells, highlights the distinctive features of ALLO-316. We believe these findings from our Phase 1 trial lay the groundwork for a new generation of allogeneic cell therapies.”

As of the October 14, 2024 data cutoff, 39 patients had been enrolled in the ongoing Phase 1 trial, of which 26 were confirmed to have CD70 positive RCC and were evaluable for efficacy outcomes. The median time from enrollment to the start of therapy was five days. Data from dose escalation cohorts and ongoing Phase 1b expansion cohort are included in the presentations. The Phase 1b expansion cohort is evaluating safety and efficacy of ALLO-316 at DL2 (80M CAR T cells) following a standard FC500 (fludarabine (30 mg/m²/day) and cyclophosphamide (500 mg/m²/d) for 3 days) lymphodepletion regimen. The Phase 1b expansion cohort is expected to ultimately include approximately 20 patients. Additional data from the Phase 1b expansion cohort is expected to be announced in mid-2025.

Following a single infusion of ALLO-316 in heavily pretreated patients, the trial demonstrated best Overall Response Rate (ORR) of 50% and Confirmed Response Rate of 33% in those patients with CD70 Tumor Proportion Score (TPS) of ≥50% who received DL2. Patients with a TPS of ≥50% comprise the majority of patients with advanced or metastatic RCC. Of those with a TPS ≥50, 76% (16/21) experienced a reduction in tumor burden. Two of six (33%) patients with high TPS who received the Phase 1b expansion regimen showed durable responses ongoing at ≥4 months.

Response Rates by CD70 Status and Dose

^aPatients evaluable for disease outcome includes those who received ALLO-316 and had at least one tumor assessment.
^bStandard fludarabine and cyclophosphamide plus ALLO-647
^cIncludes FC300 and FC500
^dBest overall response across visits did not require confirmation for CR/PR.
^eConfirmed overall response of CR/PR required confirmation at the subsequent visit.

The most common all-grade adverse events were cytokine release syndrome (CRS) (with only one grade ≥3), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%) and nausea (51%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was minimal at 8% and no graft-versus-host disease (GvHD) occurred.

Safety: Most Prevalent TEAEs (>40% Any Grade Incidence) and AESI

TEAE included all AEs that started from the first dose date of study drug in each treatment period up to start of another treatment period, death, or the date prior to initiation of another anti-cancer agent, whichever occurred first. IEC-HS includes the preferred terms IEC-HS, HLH, Hemophagocytic lymphohistiocytosis, and atypical HLH. Two patients developed an inflammatory syndrome prior to the existence of IEC-HS as a term in MedDRA, which has been updated as of September 2023.
^aInfection events (62%) were primarily low grade; the most common was viral infections (33%) with cytomegalovirus infection and COVID-19 (any grade, 18% and 15%; Grade ≥3, 0% and 5%, respectively).
^bNeurotoxicity includes system organ class of nerve system disorders and psychiatric disorders with onset date up to Study Day 30 post ALLO-316 infusion.

Two DLT events of autoimmune hepatitis and cardiogenic shock were reported. Each event occurred in 2 separate participants who received FCA (FC300 plus ALLO-647) lymphodepletion and DL2 of ALLO-316. Three Grade 5 treatment-related adverse events were reported: 1) cardiogenic shock, which was one of the 2 DLT events; 2) sepsis from multi-drug resistant Klebsiella pneumoniae in a participant who received DL4 of ALLO-316. This participant had a prior episode of muscle abscess and bacteremia from the same multi-drug resistant Klebsiella and was receiving anakinra and dexamethasone for hyperinflammation; 3) failure to thrive in a participant 16 months after treatment with ALLO-316. This subject had tumor response of stable disease (SD) at month 12 and no interval scans to evaluate disease status prior to death.

About ALLO-316 (TRAVERSE)
ALLO-316 is an AlloCAR T^™ investigational product targeting CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In October 2024 the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation based on the potential of ALLO-316 to address the unmet need for patients with advanced or metastatic RCC. The FDA previously granted Fast Track Designation (FTD) to ALLO-316 in March 2023. In April 2024, the Company announced a $15 million award from the California Institute for Regenerative Medicine (CIRM) to support the ongoing TRAVERSE trial with ALLO-316 in RCC.

About Allogene Therapeutics
Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T^™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on X and LinkedIn.

About the California Institute for Regenerative Medicine (CIRM)
At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast-track the development of today’s most promising stem cell technologies. CIRM is one of the world’s largest institutions dedicated to helping people by bringing the future of regenerative medicine closer to reality.

Cautionary Note on Forward-Looking Statements for Allogene
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as “potential,” “continue,” “plans,” “can,” “will,” “advance,” “suggest,” “appears to,” “promising,” “expected to,” “designed to,” “goal,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements are statements that are not historical facts, including statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the future development, timing, and success of clinical trials and product candidates; statements regarding the potential of ALLO-316 as a treatment for patients with advanced renal cell carcinoma (RCC); the potential for CAR T-cell therapy to treat solid tumors; the advancement of Allogene’s Dagger^® technology as a next-generation allogeneic platform; the anticipated benefits of a one-time infusion therapy; the potential for ALLO-316 to be developed across both hematologic malignancies and solid tumors; Allogene’s plans to seek additional FDA input for the clinical development of ALLO-316; and Allogene’s ability to deliver cell therapy on-demand, faster, more reliably, and at greater scale to more patients. Various factors may cause material differences between Allogene’s expectations and actual results, including, risks and uncertainties related to the ongoing clinical trial for ALLO-316 and potential adverse effects; the limited nature of our Phase 1 data from our clinical trials and the extent to which such data may or may not be validated in any future clinical trials; uncertainties regarding regulatory interactions, including future feedback from the U.S. Food and Drug Administration and implications of the RMAT designation; risks relating to the development of allogeneic cell therapy and CAR T products; the impact of competitive and market conditions; uncertainties relating to our novel technologies which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; difficulties we may encounter enrolling patients in our clinical trials; we may not be able to demonstrate the safety and efficacy of our product candidates in our clinical trials, which may prevent or delay regulatory approval and commercialization; and uncertainties regarding our ability to obtain additional financing to develop our products and implement our operating plans. These and other risks are discussed in greater detail in Allogene’s filings with the SEC, including without limitation under the “Risk Factors” heading in its Form 10-Q filed for the quarter ended June 30, 2024, filed with the SEC on August 7, 2024. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

AlloCAR T^™ and Dagger^® are trademarks of Allogene Therapeutics, Inc.

Allogene’s investigational AlloCAR T^™ oncology products utilize Cellectis technologies. The anti-CD70 AlloCAR T program is licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to this AlloCAR T^™ program.

Allogene Media/Investor Contact:
Christine Cassiano
EVP, Chief Corporate Affairs & Brand Strategy Officer
Christine.Cassiano@allogene.com